Differential somatic CAG repeat instability in variable brain cell lineage in dentatorubral pallidoluysian atrophy (DRPLA): a laser-captured microdissection (LCM)-based analysis

Hum Genet. 2000 Nov;107(5):452-7. doi: 10.1007/s004390000400.


Employing a laser-captured microdissection (LCM), we have investigated the somatic instability of CAG repeats in the variable brain cell lineage in three patients with dentatorubral pallidoluysian atrophy (DRPLA). LCM enables the isolation of single lineage brain cells for subsequent molecular analysis. We have found that CAG repeat size and the range of CAG repeats in the cerebellar granular cells is smaller than those in cerebellar glial cells. Similarly, those in the cerebral neuronal cells are significantly shorter than those in cerebral glial cells. These data directly indicate that the CAG repeat is relatively more stable in neuronal cells than in glial cells. Furthermore, cerebellar granular cells show significantly smaller main CAG repeat size and CAG repeat range than either Purkinje cells or cerebral neuronal cells, suggesting that somatic instability in the CAG repeat is markedly variable even among the different types of neuronal populations. The cell-specific CAG repeat instability may thus be more complex than has previously been considered. LCM is a powerful tool for elucidating the mechanism of the triplet repeat instability of each cell type.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Autopsy
  • Brain / metabolism
  • Brain / pathology*
  • Cell Line
  • Cerebellum / pathology*
  • Dissection / methods
  • Frontal Lobe / pathology
  • Humans
  • Middle Aged
  • Myoclonic Epilepsies, Progressive / genetics*
  • Myoclonic Epilepsies, Progressive / pathology
  • Neuroglia / pathology
  • Neurons / pathology
  • Purkinje Cells / pathology
  • Trinucleotide Repeats / genetics*